chr19-35299600-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002361.4(MAG):c.462G>A(p.Glu154Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,605,214 control chromosomes in the GnomAD database, including 53,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 12254 hom., cov: 26)

Exomes 𝑓: 0.22 ( 41702 hom. )

Consequence

MAG
NM_002361.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0520

Publications

14 publications found

Variant links:

Genes affected

MAG (HGNC:6783): (myelin associated glycoprotein) The protein encoded by this gene is a type I membrane protein and member of the immunoglobulin superfamily. It is thought to be involved in the process of myelination. It is a lectin that binds to sialylated glycoconjugates and mediates certain myelin-neuron cell-cell interactions. Three alternatively spliced transcripts encoding different isoforms have been described for this gene. [provided by RefSeq, Nov 2010]

MAG Gene-Disease associations (from GenCC):

complex hereditary spastic paraplegia
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
hereditary spastic paraplegia 75
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

MAG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 19-35299600-G-A is Benign according to our data. Variant chr19-35299600-G-A is described in ClinVar as Benign. ClinVar VariationId is 1168416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.052 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MAG	NM_002361.4 link	c.462G>A	p.Glu154Glu	synonymous_variant	Exon 5 of 11	ENST00000392213.8	NP_002352.1	P20916-1Q53ES7
MAG	NM_001199216.2 link	c.387G>A	p.Glu129Glu	synonymous_variant	Exon 5 of 11		NP_001186145.1	P20916-3
MAG	NM_080600.3 link	c.462G>A	p.Glu154Glu	synonymous_variant	Exon 5 of 12		NP_542167.1	P20916-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MAG	ENST00000392213.8 link	c.462G>A	p.Glu154Glu	synonymous_variant	Exon 5 of 11	1	NM_002361.4	ENSP00000376048.2		P20916-1

Frequencies

GnomAD3 genomes

AF:

0.346

AC:

52391

AN:

151296

Hom.:

12231

Cov.:

show subpopulations

Gnomad AFR

AF:

0.675

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.252

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.361

Gnomad SAS

AF:

0.257

Gnomad FIN

AF:

0.199

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.319

GnomAD2 exomes

AF:

0.258

AC:

62980

AN:

244250

AF XY:

0.250

show subpopulations

Gnomad AFR exome

AF:

0.680

Gnomad AMR exome

AF:

0.203

Gnomad ASJ exome

AF:

0.263

Gnomad EAS exome

AF:

0.361

Gnomad FIN exome

AF:

0.206

Gnomad NFE exome

AF:

0.209

Gnomad OTH exome

AF:

0.235

GnomAD4 exome

AF:

0.225

AC:

326661

AN:

1453800

Hom.:

41702

Cov.:

AF XY:

0.224

AC XY:

161564

AN XY:

721642

show subpopulations

African (AFR)

AF:

0.686

AC:

22812

AN:

33238

American (AMR)

AF:

0.208

AC:

9221

AN:

44340

Ashkenazi Jewish (ASJ)

AF:

0.257

AC:

6671

AN:

26002

East Asian (EAS)

AF:

0.379

AC:

14918

AN:

39350

South Asian (SAS)

AF:

0.248

AC:

21273

AN:

85608

European-Finnish (FIN)

AF:

0.201

AC:

10665

AN:

53152

Middle Eastern (MID)

AF:

0.272

AC:

1558

AN:

5718

European-Non Finnish (NFE)

AF:

0.203

AC:

224464

AN:

1106468

Other (OTH)

AF:

0.252

AC:

15079

AN:

59924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

12094

24188

36282

48376

60470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8092

16184

24276

32368

40460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.347

AC:

52467

AN:

151414

Hom.:

12254

Cov.:

AF XY:

0.344

AC XY:

25421

AN XY:

73954

show subpopulations

African (AFR)

AF:

0.674

AC:

27800

AN:

41220

American (AMR)

AF:

0.252

AC:

3836

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

862

AN:

3468

East Asian (EAS)

AF:

0.361

AC:

1810

AN:

5010

South Asian (SAS)

AF:

0.257

AC:

1232

AN:

4796

European-Finnish (FIN)

AF:

0.199

AC:

2102

AN:

10540

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.204

AC:

13864

AN:

67838

Other (OTH)

AF:

0.321

AC:

673

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1382

2765

4147

5530

6912

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

466

932

1398

1864

2330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.261

Hom.:

19261

Bravo

AF:

0.366

Asia WGS

AF:

0.358

AC:

1246

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 75

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Oct 30, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.7

(source)

DANN

Benign

0.42

PhyloP100

-0.052

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over